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United States Patent | 6,165,467 |
Hagiwara ,   et al. | December 26, 2000 |
A stabilized human monoclonal antibody preparation containing 1 to 20 mg of D-mannitol per 1 mg of a human monoclonal antibody. This preparation is excellent in stability in a solution state, a freeze drying state and a freezing state, particularly stability against aggregation and precipitation of the human monoclonal antibody at the time of redissolution after freeze drying.
Inventors: | Hagiwara; Hideaki (Takarazuka, JP); Yuasa; Hideo (Kasai, JP); Yamamoto; Yasunori (Kasai, JP) |
Assignee: | Yoshihide Hagiwara (Hyogo-Ken, JP) |
Appl. No.: | 970393 |
Filed: | November 14, 1997 |
Jul 20, 1991[JP] | 3-204743 |
Current U.S. Class: | 424/155.1; 424/142.1; 424/177.1; 530/388.15; 530/388.8; 530/390.5 |
Intern'l Class: | C07K 016/30; A61K 039/395 |
Field of Search: | 530/388.15,390.5,388.8 424/155.1,142.1,177.1 |
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225320 | Sep., 1988 | JP. |
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TABLE 1 ______________________________________ Solubility (OD.sub.600) of human monoclonal antibody after freeze drying in each stabilizer Quantity (mg) of antibody in one vial Stabilizer 0 1.0 2.5 5.0 ______________________________________ PBS 0.019 0.194 0.311 0.427 Physiological saline 0.001 0.220 0.582 0.952 for injection 1% mannitol 0.001 0.014 0.035 -- 5% mannitol 0.000 0.194 0.270 -- 10% mannitol 0.001 0.246 0.317 -- 1% mannitol + 0.001 0.193 0.228 -- physiological saline for injection Glycine-mannitol 0.010 0.042 -- 0.115 ______________________________________
TABLE 2 ______________________________________ Solubility (OD.sub.600) of human monoclonal antibody after freeze drying in D-mannitol Quantity (mg) Quantity (mg) of antibody of D-mannitol in one vial one vial 1 mg 2.5 mg 5 mg ______________________________________ 1 0.007 0.008 0.008 2 0.005 0.004 0.013 5 0.003 0.003 0.002 10 0.001 0.004 0.008 15 0.002 0.002 0.005 20 0.005 0.012 0.006 50 0.194 0.022 0.024 100 0.246 0.127 0.031 ______________________________________